Comparing Post-Treatment SPECT to PSMA PET for Radioligand Therapy Monitoring "Presentation" - Thomas Hope
April 30, 2025
At the 2025 UCSF-UCLA PSMA Conference, Thomas Hope challenges using PSMA PET/CT for restaging during radioligand therapy, advocating instead for post-treatment SPECT/CT imaging. While both modalities show the same relationship between tumor response and outcomes, SPECT can be performed after every treatment cycle, providing continuous views of disease distribution changes. Dr. Hope demonstrates how post-treatment SPECT led to management changes in about 50% of patients across various cycles.
Biography:
Thomas Hope, MD, Professor of Abdominal Imaging and Nuclear Medicine, Vice Chair of Clinical Operations and Strategy, Director of Molecular Therapy, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
Biography:
Thomas Hope, MD, Professor of Abdominal Imaging and Nuclear Medicine, Vice Chair of Clinical Operations and Strategy, Director of Molecular Therapy, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
Read the Full Video Transcript
Thomas Hope: Here are my disclosures. I'm going to start with this. This is from the EANM/SNMMI guidelines on how to perform PSMA radioligand therapy. And it says in it-- and my name is on this paper-- optimal modality for imaging-based restaging is PSMA PET/CT. Where PSMA PET is not available, PSMA SPECT or scintigraphy is possible.
So my only goal of this talk is to disprove this statement that is in a paper that many in this room are on. Why is that? A lot of the data on PSMA PET restaging is based on papers like this. You do PSMA PET at baseline, you get a PSMA PET after two cycles.
And if your volume goes down, bad things happen. If your volume goes up, good things happen-- the opposite of what I just said there. That's not too surprising that you could do that with ultrasound. You could do it with CT, MR, PET, FDG. Whatever modality you want, if your disease gets smaller, guess what, you do better. If your disease gets bigger, you do worse.
So it's not actually too helpful. Any of these diagrams is not very useful. Actually, the one on the right is even weirder. That's RPFS. And guess what, if you have progression, you progress a lot faster than the patients who don't have progression. I'm not even sure that's worth putting into an article.
Now, the interesting thing is the exact same thing is true. Not surprising with SPECT. So you can image the lutetium itself directly, right? So you get a SPECT CT of the injected lutetium, and you can image, after each cycle, what happens to the patient. And guess what, if your disease gets bigger, you do worse. If it gets smaller, you do better.
OK, exciting. Now, the reason why I want to push SPECT in this setting is cases like this. You have a patient, baseline PSMA PET. PSA is that. Then you get Cycle 1, Cycle 2, Cycle 3. And you can see here, at Cycle 2, maybe the lesion in the pelvis here is a little larger.
But these lesions in the cervical spine are getting better. So you're maybe seeing a little bit of a heterogeneous response. And then you go to the next cycle, which I don't have arrows for, so I'll go back. And the patient, frankly, progresses. But depending on where you're going to get your PSMA PET, I'm not sure what you're going to see there.
The disease is changing over each of the cycles, and you can't get repeat PSMA PETs after every single treatment. But you can, relatively easily, get post-treatment SPECT. So here is a patient baseline. And I love this case because it just shows the dynamic nature, over time, of different sites of disease in the patient.
His nodal disease, he's, in essence, 99% nodal disease. At baseline, there are a couple little osseous metastases. As you go through treatment, he, in essence, has no nodal disease by the end and is 100% osseous dominant by the end. And you can see, in the post-treatment SPECT, that dynamically happening in this patient.
And you can see heterogeneous responses, everything you want to know. And I will say, once you start looking, you'll be amazed at what you see in the patients that you are treating during therapy. Now, Surekha Yadav, who is in the audience somewhere here, did this paper looking at changes in management.
So you do post-treatment SPECTs. You see when there was a progression you didn't expect that caused you to stop treatment early. Or maybe the patient responded so well we stopped early. And you can see, in this paper, about 50% of patients had a change in management based on the post-treatment imaging.
But what I think is most interesting is, if you look over cycles-- Cycle 2, Cycle 3, Cycle 4, Cycle 5-- there's no one cycle where the change in management occurs. It happens at different times, as the patients progress at different tempos. So you can't choose a single time point when you want to do your PSMA PET to change management.
So PSMA PET is limited by the fact that you can't do it all the time. The other limitation of PSMA PET is given in this example. This is a patient. The baseline PSMA PET is this. SUVmax was 63. Looks like a good candidate for PSMA radioligand therapy. Does have liver disease.
Two months later-- or three and a half months later, they get Cycle 1. That's Cycle 1. Look at how different the distribution of disease is between a baseline PSMA PET and Cycle 1. And if you look in our cohort, the average time between baseline PSMA PET and first cycle of treatment is about three months.
We're not going to repeat a PSMA PET a week ahead of time just so we have a concurrent baseline. You just get a post-treatment SPECT. You always have a perfect baseline image with a post-treatment SPECT. Now, obviously, this patient grew quite rapidly.
But if you only got a post-treatment PET after Cycle 2, comparing back to the baseline, you wouldn't know what had happened during the course of this patient's therapy. The other thing to add here, this is a nice paper by Louise Emmett's group showing that it doesn't really matter when you do your acquisition. We do our post-treatment SPECTs one day out.
For dosimetry, it's a little more accurate than four hours. But you can do it four hours after injection and qualitatively get a very similar result. You'll miss some small lesions overall, but it does allow you to do this in a single day of treatment and the imaging on a single day, which is helpful. And I think as we move forward with post-treatment SPECT, where we're moving is to actually use this in combination with PSA response, to put in treatment delays and change the management based on how the disease is changing during the patient's treatment.
And this is, as Dr. Calais mentioned, being taken into account in his trial, the FLEX MRT trial, using post-treatment imaging plus PSA and how the patient is doing to put delays in the patients who are being treated with PSMA radioligand therapy. So my only point here is SPECT/CT should be used in place of PSMA PET.
There are a number of reasons. A, you can get it after every single cycle. It's a heck of a lot cheaper, right? You don't have to inject another radiopharmaceutical, which is the most expensive component of a PSMA PET. It gives you the same information of the PSMA PET, and it takes away the timing of your baseline imaging.
You don't have to worry about progression between your PSMA PET and Cycle 1 overall. There's one important caveat here. This is more for Professor Morris, before he notes this, is that clinical practice is very different than clinical trials. In a clinical trial, you can't use post-treatment SPECT as your progression marker.
You can use it, maybe, if you're doing personalized dosing and putting in delays. But you need standard timing on the PSMA PETs on both treatment arms in order to determine changes in RPFS. So in the clinical trial setting, you will actually need PSMA PET. But in the setting of clinical practice, we can use post-treatment SPECT.
So use post-treatment SPECT to follow patients. You'll be amazed by what you see. It's a really great modality for managing those patients with PSMA radioligand therapy. And I was short and efficient in getting on to a much more interesting talk.
Thomas Hope: Here are my disclosures. I'm going to start with this. This is from the EANM/SNMMI guidelines on how to perform PSMA radioligand therapy. And it says in it-- and my name is on this paper-- optimal modality for imaging-based restaging is PSMA PET/CT. Where PSMA PET is not available, PSMA SPECT or scintigraphy is possible.
So my only goal of this talk is to disprove this statement that is in a paper that many in this room are on. Why is that? A lot of the data on PSMA PET restaging is based on papers like this. You do PSMA PET at baseline, you get a PSMA PET after two cycles.
And if your volume goes down, bad things happen. If your volume goes up, good things happen-- the opposite of what I just said there. That's not too surprising that you could do that with ultrasound. You could do it with CT, MR, PET, FDG. Whatever modality you want, if your disease gets smaller, guess what, you do better. If your disease gets bigger, you do worse.
So it's not actually too helpful. Any of these diagrams is not very useful. Actually, the one on the right is even weirder. That's RPFS. And guess what, if you have progression, you progress a lot faster than the patients who don't have progression. I'm not even sure that's worth putting into an article.
Now, the interesting thing is the exact same thing is true. Not surprising with SPECT. So you can image the lutetium itself directly, right? So you get a SPECT CT of the injected lutetium, and you can image, after each cycle, what happens to the patient. And guess what, if your disease gets bigger, you do worse. If it gets smaller, you do better.
OK, exciting. Now, the reason why I want to push SPECT in this setting is cases like this. You have a patient, baseline PSMA PET. PSA is that. Then you get Cycle 1, Cycle 2, Cycle 3. And you can see here, at Cycle 2, maybe the lesion in the pelvis here is a little larger.
But these lesions in the cervical spine are getting better. So you're maybe seeing a little bit of a heterogeneous response. And then you go to the next cycle, which I don't have arrows for, so I'll go back. And the patient, frankly, progresses. But depending on where you're going to get your PSMA PET, I'm not sure what you're going to see there.
The disease is changing over each of the cycles, and you can't get repeat PSMA PETs after every single treatment. But you can, relatively easily, get post-treatment SPECT. So here is a patient baseline. And I love this case because it just shows the dynamic nature, over time, of different sites of disease in the patient.
His nodal disease, he's, in essence, 99% nodal disease. At baseline, there are a couple little osseous metastases. As you go through treatment, he, in essence, has no nodal disease by the end and is 100% osseous dominant by the end. And you can see, in the post-treatment SPECT, that dynamically happening in this patient.
And you can see heterogeneous responses, everything you want to know. And I will say, once you start looking, you'll be amazed at what you see in the patients that you are treating during therapy. Now, Surekha Yadav, who is in the audience somewhere here, did this paper looking at changes in management.
So you do post-treatment SPECTs. You see when there was a progression you didn't expect that caused you to stop treatment early. Or maybe the patient responded so well we stopped early. And you can see, in this paper, about 50% of patients had a change in management based on the post-treatment imaging.
But what I think is most interesting is, if you look over cycles-- Cycle 2, Cycle 3, Cycle 4, Cycle 5-- there's no one cycle where the change in management occurs. It happens at different times, as the patients progress at different tempos. So you can't choose a single time point when you want to do your PSMA PET to change management.
So PSMA PET is limited by the fact that you can't do it all the time. The other limitation of PSMA PET is given in this example. This is a patient. The baseline PSMA PET is this. SUVmax was 63. Looks like a good candidate for PSMA radioligand therapy. Does have liver disease.
Two months later-- or three and a half months later, they get Cycle 1. That's Cycle 1. Look at how different the distribution of disease is between a baseline PSMA PET and Cycle 1. And if you look in our cohort, the average time between baseline PSMA PET and first cycle of treatment is about three months.
We're not going to repeat a PSMA PET a week ahead of time just so we have a concurrent baseline. You just get a post-treatment SPECT. You always have a perfect baseline image with a post-treatment SPECT. Now, obviously, this patient grew quite rapidly.
But if you only got a post-treatment PET after Cycle 2, comparing back to the baseline, you wouldn't know what had happened during the course of this patient's therapy. The other thing to add here, this is a nice paper by Louise Emmett's group showing that it doesn't really matter when you do your acquisition. We do our post-treatment SPECTs one day out.
For dosimetry, it's a little more accurate than four hours. But you can do it four hours after injection and qualitatively get a very similar result. You'll miss some small lesions overall, but it does allow you to do this in a single day of treatment and the imaging on a single day, which is helpful. And I think as we move forward with post-treatment SPECT, where we're moving is to actually use this in combination with PSA response, to put in treatment delays and change the management based on how the disease is changing during the patient's treatment.
And this is, as Dr. Calais mentioned, being taken into account in his trial, the FLEX MRT trial, using post-treatment imaging plus PSA and how the patient is doing to put delays in the patients who are being treated with PSMA radioligand therapy. So my only point here is SPECT/CT should be used in place of PSMA PET.
There are a number of reasons. A, you can get it after every single cycle. It's a heck of a lot cheaper, right? You don't have to inject another radiopharmaceutical, which is the most expensive component of a PSMA PET. It gives you the same information of the PSMA PET, and it takes away the timing of your baseline imaging.
You don't have to worry about progression between your PSMA PET and Cycle 1 overall. There's one important caveat here. This is more for Professor Morris, before he notes this, is that clinical practice is very different than clinical trials. In a clinical trial, you can't use post-treatment SPECT as your progression marker.
You can use it, maybe, if you're doing personalized dosing and putting in delays. But you need standard timing on the PSMA PETs on both treatment arms in order to determine changes in RPFS. So in the clinical trial setting, you will actually need PSMA PET. But in the setting of clinical practice, we can use post-treatment SPECT.
So use post-treatment SPECT to follow patients. You'll be amazed by what you see. It's a really great modality for managing those patients with PSMA radioligand therapy. And I was short and efficient in getting on to a much more interesting talk.